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Introduction: We conducted a scoping review to analyze the effects and implications of vitamin D deficiency on female reproductive health during the last decade, considering temperate planetary zones and climate change impacts. Methods: We used a qualitative methodology for a panoramic database review of PubMed, Web of Science, and Scopus covering articles from the last decade focused on populations living at latitudes higher than 40° N and 40° S. As descriptors, we used the phrases climate change, cholecalciferol or vitamin d3, pregnancy, and woman health and the Boolean operators AND and OR. We excluded letters to the editor, reviews, protocols, and clinical trials without human participants, as well as duplicate articles. Results: We included 35 studies in English, the majority of which were from North America or Europe. No studies were found from the Southern Hemisphere or having any direct relation with climate change, although studies demonstrated that latitude and environmental factors affected vitamin D deficiency, which had an impact on pregnant women and their children. Supplementation guidelines were not well developed, and there was a lack of studies among at‐risk groups of women (eg, darker skin, higher latitudes, immigrants) across the life span. Discussion: Vitamin D deficiency is a global environmental problem that affects female reproductive health and depends on multiple environmental factors and human behavior. Therefore, we recommend consideration of environmental and sociocultural factors in public policy and clinical research and more research on the effectiveness of supplementation and fortification strategies. Health care professionals working in reproductive health need to generate actions for detection of, education on, and prevention of vitamin D deficiency among women across their life spans, considering the multicausality of the phenomenon, which includes environmental and climate factors in population health. [ABSTRACT FROM AUTHOR]

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Purpose: It is known that vitamin D has positive effects on graft functions (reduce fibrosis, suppress excessive inflammatory response, improve graft functions). In our study, it was aimed to evaluate the effects and predictive roles of vitamin D, the expression of vitamin D receptor (VDR) in lymphocytes, monocytes, natural killer cells on chronic rejection and graft functions in kidney transplant patients., Methods: Seventy one people were included in the study and analyses were made by dividing them into 3 groups. Group 1: Healthy control (n = 29), Group 2: Kidney transplant patients with stable kidney function (n = 17), and Group 3: Kidney transplant patients with chronic rejection diagnosis (n = 25). Serum 25-hydroxycholecalciferol, 1.25 dihydroxycholecalciferol levels and VDR percentages in CD4 + , CD8 + , CD14 + , CD56 + cells were measured in 3 groups. ROC analyses and logistic regression models were performed to predict rejection and long-term graft functions., Results: The percentage of VDR expression in CD4 + lymphocytes (p < 0.001) and CD14( +) monocytes (p < 0.001), 25-hydroxycholecalciferol and 1.25 dihydroxycholecalciferol levels were lower in group 3 was detected. In ROC analyses and logistic regression models, VDR expression in CD4( +)T lymphocytes was shown to have a statistically significant value in the development of chronic rejection (Odds ratio 0.86: 0.76-0.92; p = 0.001/AUC = 0.941, p < 0.001) and prediction of 5th-year graft functions (Odds ratio 0.93: 0.88-0.98; p = 0.017/AUC = 0.745, p = 0.007)., Conclusion: In our study, it was shown that low vitamin D and VDR expression is associated with poor outcome and VDR expression in CD4( +)T lymphocytes is predictive in terms of graft function and rejection., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

To show the association between1,25 dihydroxycholecalciferol and its effect on obesity. Background. One of the top worldwide health problems are overweight and obesity, it has reached pandemic proportions, with at least 2.8 million people dying each year as a result of being overweight or obese. In 2016,more than 1.9 billion adults, aged (18 years and older) were overweight, of these more than 650 million adults were obese. Many causes have been implicated for developing obesity such as: lack of physical activity, excessive food intake, genetic susceptibility, endocrine disorders, mental disorder, ormedications. Material and methods: One hundred andfive person were participated in this study visiting Al-Imam Al-Sadiq Teaching Hospital from October 2017 to June 2018. A 50 normal non-obese, and 55 obese. They were classified according to body mass index after measuring their weight, height, The Berlin Questionnaire was done for all patients and controls for diagnosis excluded disease and any treatment that effect on obesity. Blood and data were collected from patients and control to detectedVitamin D. Results:the highest percentage of obese patients were recorded among 20-30 age group, the majority of the obese patients were from urban areas, graduated from secondary school, unemployed. Regarding investigation: vitamin D, there is no significant difference (p value > 0.05) between patients and controls for vitamin D, also no significant correlation between vitamin D and BMI (r = 0.04, P = 0.787), waist circumference (r = 0.006, P = 0.967), waist hip ratio (r = -0.1, P = 0.495). Conclusion:there is no significant association between obesity and vitamin D. [ABSTRACT FROM AUTHOR]

Highlights • ALOX5 rs4987105 polymorphism is associated with T2D. • ALOX5 CC risk genotype is linked to lower vitamin D and increased CRP levels. • IL-1β + calcitriol treatment increased ALOX5, LTA4H and LTB4R1 mRNA expression. • ALOX5 andLTA4H mRNA expression were increased in T2D patients compared to HC. Abstract The arachidonate 5-lipoxygenase (ALOX5) pathway has been implicated in chronic inflammatory disease which may be influenced by vitamin D due to vitamin D response elements (VDRE). We investigated an ALOX5 polymorphism (rs4987105) in patients with type 2 diabetes (T2D) and the in vitro effects of calcitriol (1,25(OH) 2 D 3) on ALOX5 metabolism in monocytes of T2D patients and healthy controls (HC). 533 T2D and 473 HC were genotyped for the rs4987105 polymorphism. In addition, the 25(OH)D 3 and 1,25(OH) 2 D 3 plasma levels were measured in both cohorts. Further C-reactive protein (CRP) was determined in T2D patients. Our results demonstrate, that genotype CC and the allele C of ALOX5 rs4987105 polymorphism were more frequent in T2D compared to HC (OR = 1.44; 95% CI: 1.12–1.84; p < 0.05). Lower levels of both vitamin D metabolites (p < 0.0001 respectively) were found in the CC genotyped T2D patients compared to CC genotyped HC. In addition, CC genotyped T2D patients had higher levels of CRP compared to CT and TT genotyped T2D patients, (p < 0.01). In order to evaluate the impact of calcitriol in primary isolated monocytes, we isolated monocytes of 20 T2D patients and 20 HC. The cells were treated with 1,25(OH) 2 D 3 and interleukin-1beta (IL-1β) for 24 h. The following genes were analysed for expression changes: ALOX5, leukotriene A4 hydrolase (LTA4H), leukotriene B4 receptor type 1 (LTB4R1) and CD14. Treatment with IL-1β+1,25(OH) 2 D 3 increased ALOX5, LTA4H and LTB4R1 and CD14 mRNA in both T2D patients and HC (p < 0.0001, respectively). In addition, IL-1β+1,25(OH) 2 D 3 treatment led to higher ALOX5, LTA4H and CD14 mRNA levels in T2D patients compared to HC (p < 0.001, p < 0.05, p ≤ 0.05, respectively). In conclusion, ALOX5 rs4987105 allele C confers susceptibility to T2D, lower vitamin D metabolites and higher CRP levels complement this association. Additionally, IL-1β+1,25(OH) 2 D 3 treatment on, ALOX5, LTA4H and CD14 mRNA indicate a diabetes specific modulation. These findings identify a novel pathway in T2D potentially amenable for individualized therapeutic targeting. [ABSTRACT FROM AUTHOR]

This study was performed to evaluate the effects of hydroalcoholic extracts of Withania somnifera (WS) root, Withania coagulans (WC) fruit and 1, 25-dihydroxycholecalciferol [1, 25-(OH)2 D3] on bone mineralization, mechanical, and histological properties of broiler chickens. A total of 550 male one-day-old Ross 308 broiler chickens were randomly allotted to 55 pens, with 10 birds per pen (replicate), and reared for 42 days. A completely randomized design was used with 11 dietary treatments including a positive control diet with adequate Ca; a negative control diet (Ca concentration reduced by 30%); and a negative control diet supplemented with either WS or WC extracts at three levels (0, 75 and 150 mg/kg diet) or 1, 25-(OH)2 D3 at two different levels (0 and 0.5 µg/kg diet). Diets were given ad libitum from one to 42 day of age. Dietary treatments did not affect feed intake and feed conversion efficiency. On days 21 and 42, one bird per replicate was killed and tibiae were removed. Among the birds that were given negative control diet, the highest Ca retention values were noted in those that received 75 mg/kg WC (84.67%) or 150 mg/kg WS (83.09%) with 0.5 µg/kg 1, 25-(OH)2 D3. At 21 days of age, the highest tibia Ca values were obtained in birds fed negative control diet supplemented with 150 mg/kg WS or WC with no dietary supplementation of 1, 25-(OH)2 D3 (38.652 and 38.433 % respectively). No significant effects on tibia Ca were noted at 42 days. There were no significant differences (P>0.05) between experimental treatments for all tibia bone biomechanical properties. The addition of 75 mg/kg WS and 1, 25- (OH)2 D3 to negative control diets resulted in significant increase (P<0.05) in tibia mineralized zone width. The present study showed that dietary supplementation of WS and WC at 150 and 75 mg/kg, respectively improved Ca retention and the effects were more pronounced in the presence of 1, 25 (OH)2 D3. Administration of 150 mg/kg WS and WC had beneficial effects on bone calcification. Also, synergistic effects of WS and 1, 25-(OH)2 D3 resulted in significant increase in tibia mineralized zone width. [ABSTRACT FROM AUTHOR]

The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus. Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR. The data show elevated specific IgE and IgG1 concentrations in the blood of OVA-sensitized Cyp27b1-KO mice compared with wild-type littermates (+898 and +219%). Accordingly, more OVA-specific IgG1-secreting cells are present in spleen and fewer in the bone marrow of Cyp27b1-KO mice. Ag-specific mechanisms are suggested as the leucopoiesis is in general unchanged and activated murine B and T lymphocytes express Cyp27b1. Accordingly, elevated specific IgE concentrations in the blood of sensitized T cell-specific Cyp27b1-KO mice support a lymphocyte-driven mechanism. In an independent IgE-inducing model, i.e., intestinal infection with H. polygyrus, we validated the increase of total and specific IgE concentrations of Cyp27b1-KO compared with wild-type mice, but not those of IgG1 or IgA. We conclude that endogenous calcitriol has an impact on the regulation of IgE in vivo. Our data provide genetic evidence supporting previous preclinical and clinical findings and suggest that vitamin D deficiency not only promotes bone diseases but also type I sensitization. [ABSTRACT FROM AUTHOR]

KLF5 and nuclear factor κB (NF-κB) regulate cell proliferation and inflammation. Vitamin D signaling through vitamin D receptor (VDR) exerts anti-proliferative and anti-inflammatory actions. However, an actual relationship between KLF5, NF-κB and VDR in the inflammation and proliferation of macrophages is still unclear. Here, we showed that LPS and proinflammatory cytokines stimulate KLF5 gene expression in macrophages, and that 1, 25(OH) 2 D 3 suppresses LPS-induced KLF5 expression and cell proliferation via upregulation of VDR expression. Mechanistic studies suggested that KLF5 interacts with p50 subunit of NF-κB to cooperatively induce the expressions of positive cell cycle regulators cyclin B1 and Cdk1/Cdc2 in LPS-treated macrophages. Further studies revealed that 1, 25(OH) 2 D 3 -induced interaction of VDR with p50 decreases LPS-induced interaction of KLF5 with p50. Collectively, we identify a novel regulatory pathway in which 1, 25(OH) 2 D 3 induces VDR expression and promotes VDR interaction with p50 subunit of NF-κB, which in turn attenuates the association of KLF5 with p50 subunit of NF-κB and thus exerts anti-inflammatory and anti-proliferative effects on macrophages. [ABSTRACT FROM AUTHOR]

1,25-Dihydroxyvitamin D (1,25(OH) 2 D 3 ) has immunomodulatory activity and its deficiency correlates with rheumatoid arthritis (RA) incidence. Whether 1,25(OH) 2 D 3 modulates macrophage activation or protects against RA remains unclear. We demonstrate that 1,25(OH) 2 D 3 suppresses M1 macrophage polarization and CD80, IL-6, CXCL10, IFIT1, IFI44, and double-stranded RNA-dependent protein kinase R (PKR) expression in the macrophages of RA patients. In phorbol 12-myristate 13-acetate-induced THP-1 cells, 1,25(OH) 2 D 3 upregulates fructose-1,6-bisphosphatase 1 (FBP1) expression through direct promoter interaction. FBP1 interacts with PKR and promotes PKR ubiquitination degradation. SiR-FBP1 transfection impairs 1,25(OH) 2 D 3 action and suppresses IL-6, CXCL10, IFIT1, IFI27, and IFI44 expression in macrophages, whereas siR-PKR transfection impairs siR-FBP1 activity in 1,25(OH) 2 D 3 -treated macrophages. 1,25(OH) 2 D 3 treatment ameliorates the clinical signs of arthritis in tumor necrosis factor-transgenic mice, inhibits M1 polarization and marker expression, and promotes FBP1 expression in mononuclear cells isolated from swollen joints; thus, 1,25(OH) 2 D 3 suppresses M1 macrophage activation through FBP1/PKR and ameliorates arthritis by restoring the macrophage subtype., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Despite differences in the phamacokinetics of 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2) in man, the effects of these and their 1α-hydroxylated forms (1,25(OH)2D3 and 1,25(OH)2D2) on cellular activity of vitamin D-responsive cells have hardly been compared. We studied differences in the effects of these metabolites on cell number, gene transcription, protein expression and mineralisation of cultured human bone marrow-derived stromal cells (hBMSC) and rapidly mineralising mouse 2T3 osteoblasts. 50–1000 nM 25(OH) and 0.05–10 nM 1,25(OH)2 metabolites were used. At high concentrations, 25(OH)D2/D3 and 1,25(OH)2D2/D3 suppressed cell number in both human and mouse cells. The suppression was greater with cholecalciferol (D3) metabolites than with those of ergocalciferol (D2). In both cell types, 25(OH)D2 and 25(OH)D3 increased the expression of osteopontin, osteocalcin, collagen-1, receptor activator of nuclear factor kappa-B ligand, vitamin D receptor, CYP24A1 and CYP27B1 genes. Whereas there was little or no difference between the effects of 25(OH)D2 and 25(OH)D3 in hBMSCs, differences were observed in the magnitude of the effects of these metabolites on the expression of most studied genes in 2T3 cells. Alkaline phosphatase (ALP) activity was increased by 25(OH)D2/D3 and 1,25(OH)2D2/D3 in hBMSC and 2T3 cells, and the increase was greater with the D3 metabolites at high concentrations. In hBMSCs, mineralisation was also increased by 25(OH)D2/D3 and 1,25(OH)2D2/D3 at high concentrations, with D3 metabolites exerting a greater influence. In 2T3 cells, the effects of these compounds on mineralisation were stimulatory at low concentrations and inhibitory when high concentrations were used. The suppression at high concentrations was greater with the D3 metabolites. These findings suggest that there are differences in the effects of 25-hydroxy and 1α,25(OH)2 metabolites of D3 and D2 on human preosteoblasts and mouse osteoblasts, with the D3 metabolites being more potent in suppressing cell number, increasing ALP activity and influencing mineralisation. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the effects of piezosurgery in accelerating the movement of orthodontic alveolar bone tooth of rats and the expression mechanism of bone morphogenetic protein-2 (BMP-2). Adult male Wistar rats (n=30), with an age range of 14-15 weeks, and an average weight of 250±16 g were used. The animals were randomly divided into the control and observation groups. The rats in the control group were injected with 25-dihydroxyvitamin (1,25-dihydroxycholecalciferol) into their dental ligament. The rats in the observation group were placed with an orthodontic device between the first molar and central incisor in the maxillary. On the first day after animal treatment, piezosurgery stimulation was performed on the first molar in maxillary. The changes of the movement distance of the first molar and gum surface temperature on days 1, 3, 5, 7 and 14 were then compared. Immunohistochemical staining was performed to detect the expression of BMP-2 of periodontal tissue in the tension side of the first molar. Tooth movement distance in the observation group on days 5, 7 and 14 was significantly longer than that in the control group (p<0.05). The gum surface temperature of the observation group was elevated to some extent, peaking after 20 min. BMP-2 mRNA and protein levels in the observation group were significantly higher than those of the control group at days 3, 5, 7 and 14 (p<0.05). In conclusion, piezosurgery may significantly accelerate the movement of orthodontic alveolar bone tooth of rats and be associated with an increasing BMP-2 expression. [ABSTRACT FROM AUTHOR]

(1) Hematological malignancies are characterized by an immortalization, uncontrolled proliferation of blood cells and their differentiation block, followed by the loss of function. The primary goal in the treatment of leukemias is the elimination of rapidly proliferating leukemic cells (named blasts). However, chemotherapy, which removes proliferating blasts, also prevents the remaining immune cells from being activated. Acute leukemias affect elderly people, who are often not fit to survive aggressive chemotherapy. Therefore, there is a need of milder treatment, named differentiation therapy, which might simulate the immune system of the patient. 1,25-Dihydroxyvitamin D, or low-calcemic analogs of this compound, were proposed as supporting therapy in acute leukemias. (2) Bone marrow blasts from patients with hematological malignancies, and leukocytes from healthy volunteers were ex vivo exposed to 1,25-dihydroxyvitamin D, and then their genomes and transcriptomes were investigated. (3) Our analysis indicates that 1,25-dihydroxyvitamin D regulates in blood cells predominantly genes involved in immune response, such as CAMP (cathelicidin antimicrobial peptide), CP (ceruloplasmin), CXCL9 (C-X-C motif chemokine ligand 9), CD14 (CD14 molecule) or VMO1 (vitelline membrane outer layer 1 homolog). This concerns blood cells from healthy people, as well as blasts from patients with hematological malignancies. In addition, in one patient, 1,25-dihydroxyvitamin D significantly downregulated transcription of genes responsible for cell division and immortalization. (4) In conclusion, the data presented in this paper suggest that addition of 1,25-dihydroxyvitamin D to the currently available treatments would stimulate immune system, inhibit proliferation and reduce immortal potential of blasts.

Previously, we reported a FLucN-LXXLL+LBD-FLucC system that detects VDR ligands using split firefly luciferase techniques, ligand binding domain (LBD) of VDR, and LXXLL sequences that interact with LBD after VDR ligand binding. In vivo, 25-hydroxyvitamin D 3 (25(OH)D 3 ) and 1α,25-dihydroxyvitamin D 3 (1α,25(OH) 2 D 3 ) act as VDR ligands that bind to VDR, and regulate bone-related gene expression. Therefore, the amount of 25(OH)D 3 and 1α,25(OH) 2 D 3 are indicators of bone-related diseases such as rickets and osteoporosis. In this study, we have developed a novel LgBiT-LXXLL+LBD-SmBiT system using NanoLuc Binary Technology (NanoBiT), which has an emission intensity several times higher than that of the split-type firefly luciferase. Furthermore, by using genetic engineering techniques, we attempted to construct a novel system that can specifically detect 1α,25(OH) 2 D 3 . Because histidine residues at positions 305 and 397 play important roles in forming a hydrogen bond with a hydroxyl group at position C25 of 25(OH)D 3 and 1α,25(OH) 2 D 3 , His305 and His397 were each substituted by other amino acids. Consequently, the three mutant VDRs, H305D, H397N, and H397E were equally useful to detect 1α,25(OH) 2 D 3 specifically. In addition, among the 58 variants of the LXXLL sequences, LPYEGSLLLKLLRAPVEE showed the greatest increase in luminescence upon the addition of 25(OH)D 3 or 1α,25(OH) 2 D 3 . Thus, our novel system using NanoBiT appear to be useful for detecting native vitamin D or its derivatives., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The measurement of calcitriol [1,25(OH 2 )D], is important for the differential diagnosis of several disorders of calcium/phosphorus metabolism but is time-consuming and tricky. We measured serum calcitriol with a new automated direct assay on the Liaison XL platform in 888 healthy French Caucasian subjects aged 18–89 years, 32 patients with a surgically-proven PHPT, 32 pregnant women at the end of the first and at the end of the third trimester, and 24 dialysis patients before and after one year of supplementation with vitamin D3 or placebo. The mean calcitriol concentration (± SD) in the healthy population was 52.9 ± 14.5 ng/L with a 95% CI interval of 29–83.6 ng/L. In PHPT patients, calcitriol concentration was 81.6 ± 29.0 ng/L, 15 of them (46.9%) having a concentration > 83.6 ng/L. In pregnant women, calcitriol was 80.4 ± 26.4 ng/L at the end of the first trimester, and 113.1 ± 33.0 ng/L at the end of the third trimester, 12 (37.5%) and 26 (81.3%) of them having a calcitriol concentration > 83.6 ng/L at the first and third trimesters respectively. In 14 dialysis patients, calcitriol was 9.5 ± 7.7 ng/L and rose to 19.3 ng/L after one year of supplementation with 50,000 IU vitamin D3/month. In 10 other dialysis patients, calcitriol was 9.9 ± 2.9 ng/L and remained stable (12.4 ± 3.7 ng/L) after one year of placebo. In conclusion, this new automated calcitriol assay, in addition to presenting excellent analytical performances, gives the expected variations in patients compared to “normal” values obtained in an extensive reference population. [ABSTRACT FROM AUTHOR]

Background: Bone disorders are next to cardiovascular problems in frequency in renal transplant (RT) recipients. Reduction in 1,25-dihydroxycholecalciferol (1,25D) levels is among the reasons causing bone loss in these patients. Klotho (KL) serves as a co-receptor for fibroblast growth factor 23 (FGF23), and functions in vitamin D metabolism. KL polymorphisms have been identified in several studies, and phenylalanine to valine substitution at amino acid position 352 seemed to be important to KL function. We investigated KL F352V polymorphism and its relation with 1,25D levels in RT recipients. Methods: The study included 25 RT recipients (8 female, 17 male) and 26 (14 female, 12 male) healthy control subjects who were wild (FF) phenotypes in terms of KL F352V polymorphism. RT recipients with (FV, n = 11) and without (FF, n = 14) a heterozygote polymorphism were determined with high resolution DNA melting analysis of KL F352V polymorphism. Serum 1,25D levels were measured using the RIA method. Results: RT recipients with FV phenotype had significantly lower 1,25D levels (17.58 ± 18.38 pg/ml) compared to recipients with FF phenotype (44.91 ± 24.68 pg/ml) and control subjects (28.24 ± 12.13 pg/ml). 1,25D levels in RT recipients with FF phenotype were significantly higher than control subjects. Conclusions: KL F352V polymorphism may increase the expression of FGF23 co-receptor, KL protein and thus may decrease renal expression of 1α-hydroxylase, and/or stimulate 24-hydroxylase in RT recipients. The resultant decrease 1,25D levels may participate in bone loss in these patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Calcitriol, a powerful regulator of phosphate metabolism and immune response, is generated by 25-hydroxyvitamin D 1α-hydroxylase in the kidney and macrophages. Renal 1α-hydroxylase expression is suppressed by Klotho and FGF23, the expression of which is stimulated by calcitriol. Interferon γ (INFγ) regulates 1α-hydroxylase expression in macrophages through transcription factor interferon regulatory factor-1. INFγ-signaling includes Janus kinase 3 (JAK3) but a role of JAK3 in the regulation of 1α-hydroxylase expression and mineral metabolism has not been shown. Thus, the impact of JAK3 deficiency on calcitriol formation and phosphate metabolism was measured. Renal interferon regulatory factor-1 and 1α-hydroxylase transcript levels, serum calcitriol and FGF23 levels, intestinal phosphate absorption as well as absolute and fractional renal phosphate excretion were significantly higher in jak3 knockout than in wild-type mice. Coexpression of JAK3 increased the phosphate-induced current in renal sodium-phosphate cotransporter-expressing Xenopus oocytes. Thus, JAK3 is a powerful regulator of 1α-hydroxylase expression and phosphate transport. Its deficiency leads to marked derangement of phosphate metabolism. [ABSTRACT FROM AUTHOR]

Many malignancies are driven by mutations within the gene for fibroblast growth factor receptor 1 (FGFR1). Previously, we have shown that signal transduction from the FOP2-FGFR1 fusion protein in acute myeloid leukemia KG1 cells is responsible for a low level of expression of the vitamin D receptor gene. In this paper, we address whether other fibroblast growth factor receptors regulate the vitamin D receptor (VDR) gene. We used the human myeloid leukemia U937 and HL60 cells, the bone cancer cell line U2OS, and cell transfection methods to answer the question. For myeloid leukemia cells, overexpression of FGFRs 1-3 genes caused a shift towards monocytic differentiation; this was extracellular regulated kinase (Erk) 1,2-dependent. Overexpression of FGFRs 1-3 genes also upregulated expression of the VDR gene, further sensitizing these cells to 1,25-dihydroxyvitamin D-induced monocyte differentiation. When we increased expression in bone cells, fibroblast growth factor receptors did not upregulate VDR gene expression, nor influence the activity of VDR. Fibroblast growth factor receptors are overexpressed in many neoplasms. Therefore, it may be reasonable to use vitamin D analogs to treat these cancers, to activate VDR and drive cell differentiation., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

1. This study was carried out to investigate the effects of 1, 25-dihydroxycholecalciferol (1, 25 (OH)9 D3) and a hydroalcoholic extract of Withania somnífera (WS) root on performance, mineral retention, bone mineralisation, bone mechanical and bone histological characteristics of broiler chicks. 2. A 2 x 3 x 2 factorial experiment consisted of a positive control diet with adequate Ca and a negative control diet (Ca concentration reduced by 30%), three concentrations of WS (0, 75 and 150 mg/kg diet), and two concentrations of 1, 25 (OH)2 D3 (0 and 0.5 μg/kg diet). 3. A total of 600 male one-d-old Ross 308 broiler chicks were randomly distributed into 60 floor pens, with 10 birds each. Each treatment was replicated 5 times (50 birds). Diets were given ad libitum from one to 42 d of age. On d 21 and 42, one bird per replicate was killed and tibiae were removed. 4. Dietary treatments did not affect feed intake and feed conversion. The maximum body weight gain (2475 g) was noted in birds fed on a diet adequate in Ca and supplemented with 75 mg/kg WS. 5. The Ca and P retentions were significantly higher in birds that were given a diet with 30% less Ca. Supplementation of 150 nig/kg WS significantly improved Ca retention in birds receiving a negative control compared to those given a positive control diet (83.0% vs. 66.3%). Ca retention was significantly improved with the addition of 0.5 pg/kg 1, 25 (OH). D3 to the diet containing 75 mg/kg WS, regardless of dietary Ca concentration (79.5 vs. 73.3 and 77.9 vs. 68.9). 6. On d 21, birds that received WS had significantly higher tibia Ca compared to those of controls. No significant effects on tibia Ca were noted at 42 d. Birds given a negative control diet supplemented with 75 mg/kg WS and 0.5 μg/kg 1, 25 (OH)2 D3 displayed a similar tibia Ca compared to those given only 150 mg/kg WS. Dietary supplementation of 1, 25 (OH)2 D3significantly increased tibia Ca and tibial mineralised zone width in birds at 42 d of age. 7. Tibia shear force and stiffness were significantly increased by supplementation of WS. Administration of 1, 25 (OH)2 D3 resulted in a significantly lower width of the proliferative zone at 21 d of age. Reduction of the Ca supply significantly reduced the mineralised zone and cortical thickness at this age. 8. The present study showed that WS supplementation improved Ca retention, bone calcification and mechanical properties with no adverse effects on performance. Also, synergistic effects of WS and 1, 25 (OH)2 D3 were observed on Ca retention and bone calcification. [ABSTRACT FROM AUTHOR]

1. Chemical characterisation of an extract ofSolanum glaucophyllum(SG) leaves affirmed the predominant presence of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) glycosides. The compound 1-(ß-D-glucopyranosyl)-1α,25-dihydroxycholecalciferol was isolated for the first time from a natural source. 2. Vitamin D activity of the extract was confirmed by the calcaemic properties shown in a quail eggshell bioassay. The results suggested a 1,25(OH)2D3bioavailability of approximately 15%. 3. A broiler feeding experiment replicated in time was carried out with 6 treatments. A basic control diet containing 25 μg cholecalciferol/kg was supplemented with 2.5 and 5 μg free 1,25(OH)2D3/kg, with a product based on driedSGleaves (Panbonis) providing 10 μg of 1,25(OH)2D3-glycosides/kg, with two concentrations of anSGextract providing 8.8 and 37.8 μg of 1,25(OH)2D3-glycosides/kg. 4. Tibia breaking strength and stiffness were numerically greater in all treatment groups with free 1,25(OH)2D3and withSGproducts compared to controls, though the overall treatment effects only had probabilities in the range ofP = 0.07 toP = 0.1. Values for both characteristics increased progressively, with additions of synthetic 1,25(OH)2D3; values with the driedSGproduct were similar to those with 5 μg synthetic 1,25(OH)2D3/kg. 5. Plasma calcium was mildly elevated (P < 0.05) in treatment groups. TheSGextract treatment containing 37.8 μg 1,25(OH)2D3/kg gave the highest plasma calcium concentration and lowest bodyweight, signs of marginal hypervitaminosis D. Plasma 1,25(OH)2D3concentrations were in the normal range for all treatments. 6. Tibial dyschondroplasia occurred in only one replicate. The incidences were 31% in controls but considerably lower or zero with all other treatments. 7. Bioavailability of 1,25(OH)2D3in theSGproduct seemed to be higher in broiler chickens than in Japanese quails. 8. It is concluded that the inclusion of the driedSGproduct as a source of vitamin D3in broiler diets at a dietary concentration of 1 g/kg, providing 10 μg 1,25(OH)2D3/kg, is safe and efficacious. [ABSTRACT FROM AUTHOR]